Discovery of Peripheral kappa-Opioid Receptor Agonists as Novel Analgesics

kappa-Opioid receptor agonists with high selectivity over the g-opioid receptor and peripheral selectivity are attractive targets in the development of drugs for pain. We have previously attempted to create novel analgesics with peripheral selective kappa-opioid receptor agonist on the basis of TRK-820. In this study, we elucidated the biological properties of 17-hydroxy-cyclopropylmethyl and 10 alpha-hydroxy derivatives. These compounds were found to have better kappa-opioid receptor selectivity and peripheral selectivity than TRK-820.